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    • "ASPA deficiency is the basic cause of CD [16]. Elevated excretion of urinary NAAG was reported in ASPA-deficient patients [8] [9]. Because the neuropeptide NAAG is abundant in the brain [15] [19], whether ASPA deficiency affects brain NAAG to result in an increased excretion of urinary NAAG is not known. "
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    ABSTRACT: Aspartoacylase (ASPA)-deficient patients [Canavan disease (CD)] reportedly have increased urinary excretion of N-acetylaspartylglutamate (NAAG), a neuropeptide abundant in the brain. Whether elevated excretion of urinary NAAG is due to ASPA deficiency, resulting in an abnormal level of brain NAAG, is examined using ASPA-deficient mouse brain. The level of NAAG in the knockout mouse brain was similar to that in the wild type. The NAAG hydrolyzing enzyme, glutamate carboxypeptidase II (GCP II), activity was normal in the knockout mouse brain. These data suggest that ASPA deficiency does not affect the NAAG or GCP II level in the knockout mouse brain, if documented also in patients with CD.
    Brain Research 09/2004; 1016(2):268-71. DOI:10.1016/j.brainres.2004.05.035 · 2.83 Impact Factor
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    • "The metabolism of N-acetylaspartylglutamate (NAAG), an NAA– glutamate (Glu) adduct that is synthesized primarily in neurons, is also disturbed in CD, and NAAG aciduria has been identified in these individuals (Burlina et al., 1994). CD is a globally distributed genetic autosomally inherited recessive disease involving mutations of a gene on chromosome 17 that is responsible for production of the catabolic enzyme for NAA hydrolysis. "
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    ABSTRACT: N-Acetyl-L-aspartate (NAA) and its derivative N-acetylaspartylglutamate (NAAG) are major osmolytes present in the vertebrate brain. Although they are synthesized primarily in neurons, their function in these cells is unclear. In the brain, these substances undergo intercompartmental cycles in which they are released by neurons in a regulated fashion and are then rapidly hydrolyzed by catabolic enzymes associated with glial cells. Recently, the catabolic enzyme for NAA hydrolysis has been found to be expressed only in oligodendrocytes, and the catabolic enzyme for NAAG expressed only in astrocytes. These results indicate an unusual tricellular metabolic sequence for the synthesis and hydrolysis of NAAG wherein it is synthesized in neurons from NAA and L-glutamate, hydrolyzed to NAA and L-glutamate by astrocytes, and further hydrolyzed to L-aspartate and acetate by oligodendrocytes. Since the discovery that the NAA and NAAG anabolic products of neurons are specifically targeted to oligodendrocytes and astrocytes, respectively, this unique metabolic compartmentalization also suggests that these substances may play an important role in cell-specific glial signaling. In this review, it is hypothesized that a key function of NAA and NAAG in the vertebrate brain is in cell signaling and that these substances are important in the regulation of interactions of brain cells and in the establishment and maintenance of the nervous system.
    Journal of Neurochemistry 09/2000; 75(2):453-9. DOI:10.1046/j.1471-4159.2000.0750453.x · 4.24 Impact Factor
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    • "NAAG, a very abundant brain neuropeptide (Tsai and Coyle, 1995), exhibits mixed agonist/antagonist-like behaviors atexcitatory amino acid receptors, including the N-methyl-D-aspartate subtype (Blakely and Coyle, 1988; Burlina et al., 1994a). Patients afflicted with Canavan's disease, a demyelinating disease, are characterized by a deficiency of the NAA-hydrolyzing enzyme aspartoacylase (Matalon et al., 1995) and show accumulations of NAA (Matalon et al., 1995) and NAAG (Burlina et al., 1994b) in body fluids. Mast cells are pleiotropic bone marrow-derived immune cells present in connective tissues of various organs and in the nervous system (Purcell and Atterwill, 1995; Silver et al., 1996). "
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    ABSTRACT: Mast cells play a central role in both immediate allergic reactions and inflammation. A functional nerve-mast cell interaction has been proposed, given the morphological association between mast cells and neuropeptide-containing peripheral nerves. We now show that purified rat peritoneal mast cells contain large quantities of N-acetylaspartate (NAA; 747.50 nmol/mg of protein). Mast cell levels of NAA were rapidly reduced, by 64.0 and 86.4%, following treatment with compound 48/80 and mastoparan, respectively. These secretagogues strongly decreased mast cell histamine content over the same time period, suggesting also that NAA is stored in secretory granules. The data are the first to show that NAA is present in an immune effector cell type. Because NAA may be involved in myelin synthesis and glutamyl peptide metabolism, NAA released from mast cells following nervous or other stimuli could participate in neuroimmune interactions. Mast cells in multiple sclerosis plaques may contribute to the reported elevations in brain NAA in this disease.
    Journal of Neurochemistry 08/1997; 69(3):1314 - 1317. DOI:10.1046/j.1471-4159.1997.69031314.x · 4.24 Impact Factor